Signal transduction through the B cell immunoglobulin receptor is now known to involve interconnecting enzyme pathways, catalyzed by tyrosine kinase and phospholipase C. The first enzyme system utilizes 3 src family kinases, Blk, Fyn and Lyn, to phosphorylate a number of proteins on tyrosine residues following receptor crosslinking. One of the substrates has been identified as the proto-oncogene vav. Vav co- precipitates with all of the src kinases found in B lymphocytes and has an intrinsic tyrosine kinase activity associated with it. Another substrate that has been examined is a 72 Kd protein that is phosphorylated when the cells are stimulated with anti-IgD but not anti- IgM, this protein is maximally phosphorylated by approx. 20 seconds and then dephosphorylated by 1 minute. This substrate has not been identified yet but, since, only 1% of phosphorylated proteins are phosphorylated on tyrosine and since this is rapidly dephosphorlated taken together this implies that this 72 Kd protein is potentially a regulatory protein. We are attempting to clone out this gene using both a consensus sequence for tyrosine phosphorylation and also using a sutraction library. We have had a moderate amount of success to date and have found that the gene is present in a number of tumor viruses in an anti-sence form suggesting that the virus uses this gene to disrupt normal cell function.